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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/336| Epigenome-wide association study of seizures in childhood and adolescence | |
| Charlie Hatcher Esther Walton Rosa Mulder Charlotte Cecil Doretta Caramaschi Janine Felix Caroline Relton | |
| Novel Coronavirus | |
| Acceso Abierto | |
| Atribución | |
| 10.1101/19005116 | |
| The occurrence of seizures in childhood is often associated with neurodevelopmental impairments and school underachievement. Common genetic variants associated with epilepsy have been identified and epigenetic mechanisms have also been suggested to play a role. In this study we analysed the association of genome-wide blood DNA methylation with the occurrence of seizures in ~800 children from the Avon Longitudinal Study of Parents and Children, UK, at birth (cord blood), during childhood and adolescence (peripheral blood). We also analysed the association between the lifetime occurrence of any seizures before age 13 with blood DNA methylation levels. We sought replication of the findings in the Generation R Study and explored causality using Mendelian randomization, i.e. using genetic variants as proxies. The results showed five CpG sites which were associated cross-sectionally with seizures either in childhood or adolescence (1-5% absolute methylation difference at pFDR<0.05), although the evidence of replication in an independent study was weak. One of these sites was located in the BDNF gene, which is highly expressed in the brain, and showed high correspondence with brain methylation levels. The Mendelian randomization analyses suggested that seizures might be causal for changes in methylation rather than vice-versa. In addition, seizure-associated methylation changes could affect other outcomes such as growth, cognitive skills and educational attainment. In conclusion, we present a link between seizures and DNA methylation which suggests that DNA methylation changes might mediate some of the effects of seizures on growth and neurodevelopment. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The UK Medical Research Council and Wellcome (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and Doretta Caramaschi will serve as guarantors for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). GWAS data was generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. Methylation data in the ALSPAC cohort were generated as part of the UK BBSRC funded (BB/I025751/1 and BB/I025263/1) Accessible Resource for Integrated Epigenomic Studies (ARIES, http://www.ariesepigenomics.org.uk). D.C., C.R. and E.W. are funded by UK Medical Research Council (grant numbers: MC_UU_00011/1 and MC_UU_00011/5). C.H. is supported by a 4-year studentship fund from the Wellcome Trust Molecular, Genetic and Lifecourse Epidemiology Ph.D. programme at the University of Bristol (108902/B/15/Z). The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam. The generation and management of the Illumina 450K methylation array data (EWAS data) for the Generation R Study was executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, the Netherlands. The general design of the Generation R Study is made possible by financial support from the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development and the Ministry of Health, Welfare and Sport. The EWAS data was funded by a grant from the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA; project nr. 050-060-810), by funds from the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, and by a grant from the National Institute of Child and Human Development (R01HD068437). J.F.F. has received funding from the European Unions Horizon 2020 research and innovation programme under grant agreement No 633595 (DynaHEALTH) and from the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, NutriPROGRAM project, ZonMw the Netherlands no.529051022). C.C. has received funding from the European Unions Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 707404. This project received funding from the European Unions Horizon 2020 research and innovation programme (733206, LIFECYCLE). ### Author Declarations All relevant ethical guidelines have been followed and any necessary IRB and/or ethics committee approvals have been obtained. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes Any clinical trials involved have been registered with an ICMJE-approved registry such as ClinicalTrials.gov and the trial ID is included in the manuscript. Not Applicable I have followed all appropriate research reporting guidelines and uploaded the relevant Equator, ICMJE or other checklist(s) as supplementary files, if applicable. Not Applicable The ALSPAC study website contains details of all the data that is available through a fully searchable data dictionary and variable search tool. <http://www.bris.ac.uk/alspac/researchers/data-access/data-dictionary/> | |
| Cold Spring Harbor Laboratory Press | |
| 2019 | |
| Preimpreso | |
| https://www.medrxiv.org/content/10.1101/19005116v1 | |
| Inglés | |
| VIRUS RESPIRATORIOS | |
| Aparece en las colecciones: | Artículos científicos |
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| Epigenome wide.pdf | 1.44 MB | Adobe PDF | Visualizar/Abrir |